title: Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis.
abstract: BACKGROUND
  The phytosterol guggulsterone is a potent anti-inflammatory mediator with less side effects than classic steroids. This study assesses the impact of guggulsterone on tissue factor (TF) expression and thrombus formation.
  
  
  RESULTS
  Guggulsterone inhibited TNF-alpha-induced endothelial TF protein expression and surface activity in a concentration-dependent manner; in contrast, dexamethasone did not affect TNF-alpha-induced TF expression. Guggulsterone enhanced endothelial tissue factor pathway inhibitor and impaired plasminogen activator inhibitor-1 as well as vascular cell adhesion molecule-1 protein. Real-time polymerase chain reaction revealed that guggulsterone inhibited TNF-alpha-induced TF mRNA expression; moreover, it impaired activation of the MAP kinases JNK and p38, while that of ERK remained unaffected. In vivo, guggulsterone inhibited TF activity and photochemical injury induced thrombotic occlusion of mouse carotid artery. Guggulsterone also inhibited TF expression, proliferation, and migration of vascular smooth muscle cells in a concentration-dependent manner.
  
  
  CONCLUSIONS
  Guggulsterone inhibits TF expression in vascular cells as well as thrombus formation in vivo; moreover, it impairs vascular smooth muscle cell activation. Hence, this phytosterol offers novel therapeutic options, in particular in inflammatory diseases associated with an increased risk of thrombosis.
authors.affiliation: Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gebhard
authors.forename: Simon F
authors.initials: SF
authors.lastname: Stämpfli
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Gebhard
authors.forename: Alexander
authors.initials: A
authors.lastname: Akhmedov
authors.forename: Alexander
authors.initials: A
authors.lastname: Breitenstein
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.forename: Erik W
authors.initials: EW
authors.lastname: Holy
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002341:Carotid Artery Thrombosis / Q000517:prevention & control*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010840:Phytosterols / Q000494:pharmacology*; D011282:Pregnenediones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000096:biosynthesis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D010840:Phytosterols; D011282:Pregnenediones; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; C023617:pregna-4,17-diene-3,16-dione; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4